Creation of Room-Temperature Sub-100 nm Antiferromagnetic Skyrmions in an Antiferromagnet IrMn through Interfacial Exchange Coupling.

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

Category of upper eyelid morphology and the preferred double eyelid shape in Asians according to questionnaire survey.

BACKGROUND: The morphological classification of the upper eyelid in Asian people is complex and diverse and usually not consistent with what we know well. AIMS: To improve the classification of upper eyelid morphology and investigate the preferred double eyelid shape by Asian people. METHODS: An investigation of 640 patients' preferences for double eyelid shape was conducted, and the pre- and post-operative effects were assessed. The shapes of the natural eyelids of 247 people (485 eyes) who provided real photographs of the eyelids were counted. The chi-square test was used to analyze the differences. RESULTS: There were 10 eyelid shapes: single eyelid, parallel-shaped double eyelid, fan-shaped double eyelid, parallel fan-shaped double eyelid, opened fan-shaped double eyelid, crescent-shaped double eyelid, hidden-shaped double eyelid, horizontal-shaped double eyelid, triangle-shaped double eyelid, and multiple-fold eyelid. The difference in the shape of the natural eyelid between males and females was statistically significant (p < 0.05). The most popular eyelid shapes were single eyelid (24.9%), open fan-shaped double eyelid (21.0%), fan-shaped double eyelid (16.3%), and hidden-shaped double eyelid (12.6%). Men and women preferred a parallel fan-shaped double eyelid (18.0%), a parallel-shaped double eyelids (17.0%), and an open fan-shaped double eyelids (18.1%). CONCLUSIONS: The most popular upper eyelid shapes were single eyelid, open fan-shaped double eyelid, and fan-shaped double eyelid. The parallel fan-shaped, parallel-shaped, and open fan-shaped double eyelid were favored by men and women.

The Snapdragon Genomes Reveal the Evolutionary Dynamics of the S-Locus Supergene.

The genus Antirrhinum has been used as a model to study self-incompatibility extensively. The multi-allelic S-locus, carrying a pistil S-RNase and dozens of S-locus F-box (SLF) genes, underlies the genetic control of self-incompatibility (SI) in Antirrhinum hispanicum. However, there have been limited studies on the genomic organization of the S-locus supergene due to a lack of high-quality genomic data. Here, we present the chromosome-level reference and haplotype-resolved genome assemblies of a self-incompatible A. hispanicum line, AhS7S8. For the first time, 2 complete A. hispanicum S-haplotypes spanning ∼1.2 Mb and containing a total of 32 SLFs were reconstructed, whereas most of the SLFs derived from retroelement-mediated proximal or tandem duplication ∼122 Mya. Back then, the S-RNase gene and incipient SLFs came into linkage to form the pro-type of type-1 S-locus in the common ancestor of eudicots. Furthermore, we detected a pleiotropic cis-transcription factor (TF) associated with regulating the expression of SLFs, and two miRNAs may control the expression of this TF. Interspecific S-locus and intraspecific S-haplotype comparisons revealed the dynamic nature and polymorphism of the S-locus supergene mediated by continuous gene duplication, segmental translocation or loss, and TE-mediated transposition events. Our data provide an excellent resource for future research on the evolutionary studies of the S-RNase-based self-incompatibility system.

Transdermal drug delivery via microneedles to mediate wound microenvironment.

Cutaneous wound healing is a complex process, while modulating the wound microenvironment has become an essential therapeutic goal. In clinics, advanced dressings or dermal templates can promote wound healing but their ability in mediating wound microenvironment is limited. In the last decade, microneedle (MN) array patches have emerged as a new class of wound dressings. These dressings enable non-invasive transdermal and precise medication delivery. Combined with smart materials, MN additionally allows real-time monitoring of wound site markers such as inflammatory factors, oxygen levels, vascularization, pH and temperature, etc., while releasing therapeutic molecules responsively to the wound site. In this review, the MN-based strategies were reviewed for modulating wound microenvironment via introducing the main characteristics of the wound microenvironment and various types of MN-based delivery systems. Additionally, the progress and future trends in the application of MNs in mediating wound microenvironments are also discussed.

Comprehensive Study of the Current-Induced Spin-Orbit Torque Perpendicular Effective Field in Asymmetric Multilayers.

The spin-orbit torques (SOTs) in the heavy metal (HM)/ferromagnetic metal (FM) structure hold promise for next-generation low-power and high-density spintronic memory and logic applications. For the SOT switching of a perpendicular magnetization, an external magnetic field is inevitable for breaking the mirror symmetry, which is not practical for high-density nanoelectronics applications. In this work, we study the current-induced field-free SOT switching and SOT perpendicular effective field (Hzeff) in a variety of laterally asymmetric multilayers, where the asymmetry is introduced by growing the FM layer in a wedge shape. We show that the design of structural asymmetry by wedging the FM layer is a universal scheme for realizing field-free SOT switching. Moreover, by comparing the FM layer thickness dependence of (Hzeff) in different samples, we show that the efficiency (ß =Hzeff/J, J is the current density) is sensitive to the HM/FM interface and the FM layer thickness. The sign of ß for thin FM thicknesses is related to the spin Hall angle (θSH) of the HM layer attached to the FM layer. ß changes its sign with the thickness of the FM layer increasing, which may be caused by the thickness dependence of the work function of FM. These results show the possibility of engineering the deterministic field-free switching by combining the symmetry breaking and the materials design of the HM/FM interface.

Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice.

Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality. The underlying mechanism of infections has been widely investigated by scientist, while standard wound management is routinely been used in general practice. However, strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization, delayed healing and drug resistance. In the present review, we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis, non-surgical methods and surgical methods. Moreover, we highlight emerging innovations in the development of antimicrobial peptides, phages, controlled drug delivery, wound dressing materials and herbal medicine, and find that sensitive diagnostics, combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.

Quasi-one-dimensional metallic conduction channels in exotic ferroelectric topological defects.

Ferroelectric topological objects provide a fertile ground for exploring emerging physical properties that could potentially be utilized in future nanoelectronic devices. Here, we demonstrate quasi-one-dimensional metallic high conduction channels associated with the topological cores of quadrant vortex domain and center domain (monopole-like) states confined in high quality BiFeO3 nanoislands, abbreviated as the vortex core and the center core. We unveil via the phase-field simulation that the superfine metallic conduction channels along the center cores arise from the screening charge carriers confined at the core region, whereas the high conductance of vortex cores results from a field-induced twisted state. These conducting channels can be reversibly created and deleted by manipulating the two topological states via electric field, leading to an apparent electroresistance effect with an on/off ratio higher than 103. These results open up the possibility of utilizing these functional one-dimensional topological objects in high-density nanoelectronic devices, e.g. nonvolatile memory.

Tuning ferroelectricity and ferromagnetism in BiFeO3/BiMnO3 superlattices.

Multiferroic materials with multifunctional characteristics play a critical role in the field of microelectronics. In a perovskite oxide, ferroelectric polarization and ferromagnetism usually cannot coexist in a single-phase material at the same time. In this work, we design a superlattice structure composed of alternating BiFeO3 and BiMnO3 layers and illustrate how tuning the supercell size of epitaxial BiFeO3/BiMnO3 superlattices facilitates ferroelectric polarization while maintaining relatively strong ferromagnetism. A comprehensive investigation reveals that the enhanced ferroelectric polarization of BiMnO3 layers originates from the induction effect induced by a strong polarization field generated by the adjacent ferroelectric BiFeO3 layers. For the magnetic behavior, we consider the existence of interfacial antiferromagnetic superexchange interaction of Fe-O-Mn between BiFeO3 and BiMnO3 layers in our superlattices. This modulation effect of artificial superlattices provides a platform to accurately control the multiple order parameters in a multiferroic oxide system.

Nanoscale Topotactic Phase Transformation in SrFeOx Epitaxial Thin Films for High-Density Resistive Switching Memory.

Resistive switching (RS) memory has stayed at the forefront of next-generation nonvolatile memory technologies. Recently, a novel class of transition metal oxides (TMOs), which exhibit reversible topotactic phase transformation between insulating brownmillerite (BM) phase and conducting perovskite (PV) phase, has emerged as promising candidate materials for RS memories. Nevertheless, the microscopic mechanism of RS in these TMOs is still unclear. Furthermore, RS devices with simultaneously high density and superior memory performance are yet to be reported. Here, using SrFeOx as a model system, it is directly observed that PV SrFeO3 nanofilaments are formed and extend almost through the BM SrFeO2.5 matrix in the ON state and are ruptured in the OFF state, unambiguously revealing a filamentary RS mechanism. The nanofilaments are ≈10 nm in diameter, enabling to downscale Au/SrFeOx /SrRuO3 RS devices to the 100 nm range for the first time. These nanodevices exhibit good performance including ON/OFF ratio as high as ≈104 , retention time over 105 s, and endurance up to 107 cycles. This study significantly advances the understanding of the RS mechanism in TMOs exhibiting topotactic phase transformation, and it also demonstrates the potential of these materials for use in high-density RS memories.

Recyclable and Flexible Starch-Ag Networks and Its Application in Joint Sensor.

Flexible transparent conductive electrodes are essential component for flexible optoelectronic devices and have been extensively studied in recent years, while most of the researches are focusing on the electrode itself, few topics in material green and recyclability. In this paper, we demonstrate a high-performance transparent conductive electrode (TCE), based on our previous cracking technology, combined with a green and recyclable substrate, a starch film. It not only shows low Rs (less than 1.0 Ω sq-1), high transparency (> 82%, figure of merit ≈ 10,000), but also provides an ultra-smooth morphology and recyclability. Furthermore, a series of biosensors on human joints are demonstrated, showing great sensitivity and mechanical stability.

The significance of changes in platelet concentration during the early phase after severe burn injury in a Chinese mass casualty.

BACKGROUND: Changes in platelet concentration are common in severe burn patients. Platelets play a key role in the course of disease. This study aims to explore the significance of platelet concentration during the course of the disease in victims of a mass burn casualty. METHODS: A total of 180 patients were involved in the "8.2" Kunshan explosion accident in China. The examined data included age, gender, total burn area (% TBSA), third-degree burn area (% TBSA), and platelet concentration within the first 5 days after the burn injury. The patients were divided into two groups according to four indicators (resuscitation, acute respiratory distress syndrome, acute kidney injury, septic shock). We collected several types of data for the patients and divided the patients into a complication group and non-complication group according to the diagnostic criteria. We analyzed the platelet concentration of the two groups using t tests to determine whether significant differences were present. P values < 0.05 were considered statistically significant. RESULTS: The group with successful resuscitation had higher platelet concentration than the failure group on day 3 and day 5. The patients who suffered from acute kidney injury (AKI) and septic shock had a lower platelet concentration than non-sufferers on day 3 and day 5. CONCLUSIONS: The platelet concentration of burn patients can dynamically reflect the pathophysiological changes of the body. It can be used as an early objective indicator of prognosis in mass burn casualty cases.

Anti-inflammative effect of glycyrrhizin on rat thermal injury via inhibition of high-mobility group box 1 protein.

AIM: Glycyrrhizin (Gly) has been reported as an inhibitor of extracellular HMGB1 (high-mobility group box 1 protein) cytokine's activity, and protects spinal cord, liver, heart and brain against ischemia-reperfusion-induced injury in rats. The purpose of this study was to investigate the protective effect of Gly in rat skin thermal injury model and to elucidate the underlying mechanisms. METHODS: Twenty-four male Sprague-Dawley rats (200-250g) were randomly divided into control group, vehicle-treated and Gly-treated burn groups, each group contained eight animals. In the latter two groups, rats were subjected to 30% TBSA (Total Body Surface Area) full-thickness scald injury. In Gly-treated burn group, glycyrrhizin (60mg/kg) was administered intraperitoneally immediately after and at 24th hour burn; in vehicle-treated burn group, Ringer's solution (4ml/kg, as a vehicle) was administered intraperitoneally immediately after and at 24th hour burn. The animals were sacrificed at 48h after injury. Aortic blood samples were obtained to detect tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) with ELISA (Enzyme-Linked Immuno Sorbent Assay) kits. Lung, liver and kidney tissue samples were collected to determine the expression of HMGB1 mRNA and protein. HMGB1 mRNA level was semiquantitatively measured by Real-Time PCR using ß-actin as an internal standard, and protein expression of HMGBI was determined by Western blot. RESULTS: Severe skin scald injury caused a significant increase in plasma TNF-α and IL-1ß versus the control group (P<0.001) in 48h after burns. Intraperitoneal administration of Gly (60mg/kg) significantly reduced the levels of serum TNF-α and IL-1ß (P<0.01). Gly treatment reduced these biochemical indices accompanied by lower level of HMGB1 protein (P<0.05) and mRNA expression (P<0.01). CONCLUSION: These results demonstrate that Gly possesses an anti-inflammation effect to protect the remote organs from burn-induced injury.

Inhibition of oxygen-glucose deprivation-induced apoptosis of human adipose-derived stem cells by genetic modification with antiapoptotic protein bcl-2.

BACKGROUND: Adipose-derived stem cells (ADSCs) have become a promising tool for a wide range of cell-based therapies. However, transplanted ADSCs do not survive well under ischemic conditions. In this study we aimed to inhibit oxygen-glucose deprivation (OGD)-induced apoptosis of human ADSCs by genetic modification with antiapoptotic protein Bcl-2. METHODS: After isolation and culture, the phenotypes of human ADSCs at passage 3 were analyzed by flow cytometry. Then, genetic modification of ADSCs with Bcl-2 was carried out. Bcl-2 gene transfection was verified by Western blot analysis and multipotent differentiation properties were evaluated in Bcl-2-modified ADSCs (Bcl-2-ADSCs). Apoptosis was evaluated by a TUNEL assay under ischemic conditions induced by OGD. Apoptotic nuclei were also assessed and quantified by Hoechst staining. RESULTS: The cultured ADSCs expressed stem cell-associated markers CD29, CD34, CD44, and CD90, but not fibroblast marker HLA-DR or hematopoietic stem cell marker CD133. The Bcl-2 gene was transferred into ADSCs efficiently, and Bcl-2-ADSCs differentiated into adipocytes, chondrocytes, and osteoblasts. In addition, Bcl-2 overexpression reduced the percentage of apoptotic Bcl-2-ADSCs by 38 % under OGD. CONCLUSION: Our results indicate that Bcl-2 overexpression through gene transfection inhibits apoptosis of ADSCs under ischemic conditions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Fatal eosinophilic myocarditis develops in the absence of IFN-γ and IL-17A.

CD4(+) T cells play a central role in inflammatory heart disease, implicating a cytokine product associated with Th cell effector function as a necessary mediator of this pathophysiology. IFN-γ-deficient mice developed severe experimental autoimmune myocarditis (EAM), in which mice are immunized with cardiac myosin peptide, whereas IL-17A-deficient mice were protected from progression to dilated cardiomyopathy. We generated IFN-γ(-/-)IL-17A(-/-) mice to assess whether IL-17 signaling was responsible for the severe EAM of IFN-γ(-/-) mice. Surprisingly, IFN-γ(-/-)IL-17A(-/-) mice developed a rapidly fatal EAM. Eosinophils constituted a third of infiltrating leukocytes, qualifying this disease as eosinophilic myocarditis. We found increased cardiac production of CCL11/eotaxin, as well as Th2 deviation, among heart-infiltrating CD4(+) cells. Ablation of eosinophil development improved survival of IFN-γ(-/-)IL-17A(-/-) mice, demonstrating the necessity of eosinophils in fatal heart failure. The severe and rapidly fatal autoimmune inflammation that developed in the combined absence of IFN-γ and IL-17A constitutes a novel model of eosinophilic heart disease in humans. This is also, to our knowledge, the first demonstration that eosinophils have the capacity to act as necessary mediators of morbidity in an autoimmune process.

Improved location technology of perforators of anterolateral thigh flap for Chinese patients.

BACKGROUND: The anterolateral thigh (ALT) flap has been widely used in reconstruction of soft tissue defects. The anatomic variations of perforators increase the difficulties of flap elevation. The ABC system has been described for locating the most common three perforators in Western populations. Less evidence has been found regarding whether it is suitable for Chinese population. The purpose of this study is to explore the improvement of preoperative location technology and flap design for Chinese people. METHODS: Detection for perforator signals on the bilateral thigh surface was perfromed on 50 Chinese adults using handheld Doppler. Define the A-P line as the line between the anterior superior iliac spin (ASIS) and the superolateral corner of the patella (P). We defined a coordinate system on the thigh surface to record the data of each signal point. The A-P line was y-axis in this coordinate system, and the midpoint of the line was the zero point. The data of these signals were recorded in the form of coordinates. Statistics and mathematic methods were used to analyze the regularity of signal distribution and the correlation between body mass index (BMI) and signal distribution. The findings were applied in five patients who underwent the ALT flap transplantation to confirm its clinical value. RESULTS: The results showed that most of the signals appeared near the A-P line. Most signals were located 1 cm lateral (mean 0.5 cm lateral) to the A-P line. The mean vertical distance between perforator B and perforators A and C was 4 cm. More perforator signals were detected at the two horizontal level (as shown in the picture above) than other horizontal levels. The rate of accurate preoperative detection was 40% (6 of 15 perforators) and the error rate was 20% (3 of 15 perforators). The mean deviation was 1.34 cm, which is acceptable for clinical application. The mean vertical distance between perforator B and perforators A and C in clinical study (4.81 cm) corresponded to the finding of the Doppler study (4.2 cm), whereas the mean distance between perforators and the A-P line (1.57 cm) was more than the Doppler finding (0.48 cm). CONCLUSION: The A-P line is still a reliable guiding line for Doppler detection and flap design. The ABC system is suitable for the Chinese population but must be adjusted: perforator B is marked first at the midpoint and 0.5 cm lateral to the A-P line and perforators A and C are marked 4 cm distal and proximal to perforator B, respectively. In designing the flap, the region 3 cm around point B and the region between the two horizontal planes at point B and 4 cm lower should both be contained into the flap, no matter what the finding of Doppler detection is.

Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc(-/+) mice.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Colorectal cancers have a prolonged latency following initiation that may span decades providing ample time for implementing a chemoprevention strategy that could block or reverse the progression to CRC. Cdk4 pathway alterations have been linked to a number of cancers including CRC. In these experiments we focused on the Cdk4 pathway and its role in intestinal tumorigenesis as a possible target in chemoprevention strategies. METHODS: We evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor formation by crossing Cdk4(-/-) mice to Apc(-/+) mice. In addition, we tested the effect of the dietary compound silibinin on the Cdk4 pathway in Apc(-/+) mice and HT-29 colon cancer cells in culture. RESULTS: Cdk4(-/-) mice backcrossed to Apc(-/+) mice reduced intestinal adenoma formation compared to Apc(-/+) controls. Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a result silibinin blocked the development of intestinal adenomas by 52% in this genetic model (Apc(-/+) mice) of early events in colorectal cancer formation. No toxic abnormalities were detected in mice which received silibinin. CONCLUSIONS: Modification of the Cdk4 pathway using a natural plant-derived compound such as silibinin may be a useful chemopreventive strategy for colorectal carcinomas.

[Aesthetic effect of wound repair with flaps].

OBJECTIVE: To investigate the aesthetic effect of wound repair with flaps. METHODS: One thousand nine hundred and ninety-six patients with 2082 wounds hospitalized from January 2004 to December 2011. These wounds included 503 deep burn wounds, 268 pressure sores, 392 soft tissue defects caused by trauma, 479 soft tissue defects due to resection of skin cancer and mole removal, 314 soft tissue defects caused by scar excision, and 126 other wounds. Wound area ranged from 1.5 cm x 1.0 cm to 30.0 cm x 22.0 cm. Sliding flaps, expanded flaps, pedicle flaps, and free flaps were used to repair the wounds in accordance with the principle and timing of wound repair with flaps. RESULTS: Five flaps showed venous congestion within 48 hours post-operation, 2 flaps of them improved after local massage. One flap survived after local heparin wet packing and venous bloodletting. One flap survived after emergency surgical embolectomy and bridging with saphenous vein graft. One flap showed partial necrosis and healed after skin grafting. The other flaps survived well. One thousand three hundred and twenty-one patients were followed up for 3 months to 2 years, and flaps of them were satisfactory in shape, color, and elasticity, similar to that of normal skin. Some patients underwent scar revision later with good results. CONCLUSIONS: Application of suitable flaps in wound repair will result in quick wound healing, good function recovery, and satisfactory aesthetic effect.

Macrophages participate in IL-17-mediated inflammation.

The involvement of macrophages (MΦs) in Th17-cell responses is still poorly understood. While neutrophils are thought to be the predominant effector of Th17-cell responses, IL-17 is also known to induce myelotropic chemokines and growth factors. Other T-cell-derived cytokines induce non-classical functions, suggesting that IL-17 sigxnaling may similarly elicit unique MΦ functions. Here, we characterized the expression of subunits of the IL-17 receptor on primary murine MΦs from different anatomical compartments. The greatest expression of IL-17 receptors was observed on mucosal Ly6C(hi) "inflammatory" MΦs. We further observed upregulation of IL-17 receptors in vitro on bone marrow-derived macrophages (BMMΦs) in response to peptidoglycan or CpG oligonucleotide stimuli, and in vivo, upon CFA administration. Macrophages expressing IL-17 receptors were observed infiltrating the hearts of mice with myocarditis, and genetic ablation of IL-17RA altered MΦ recruitment. Treating primary MΦs from a wide variety of different anatomic sources (as well as cell lines) with IL-17A induced the production of unique profiles of cytokines and chemokines, including GM-CSF, IL-3, IL-9, CCL4/MIP-1ß and CCL5/RANTES. IL-17A also induced production of IL-12p70; IL-17-signaling-deficient MΦs elicited diminished IFN-γ production by responding DO11.10 CD4(+) T cells when used as APCs. These data indicate that MΦs from different anatomic locations direct IL-17-mediated responses.

Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy.

RATIONALE: One-third of myocarditis cases progresses to dilated cardiomyopathy (DCM), but the mechanisms controlling this process are largely unknown. CD4(+) T helper (Th)17 cells have been implicated in the pathogenesis of autoimmune diseases, but the role of Th17-produced cytokines during inflammation-induced cardiac remodeling has not been previously studied. OBJECTIVE: We examined the importance of interleukin (IL)-17A in the progression of myocarditis to DCM using a mouse model. METHODS AND RESULTS: Immunization of mice with myocarditogenic peptide in complete Freund's adjuvant induced the infiltration of IL-17A-producing Th17 cells into the inflamed heart. Unexpectedly, IL-17A-deficient mice developed myocarditis with similar incidence and severity compared to wild-type mice. Additionally, IL-17A deficiency did not ameliorate the severe myocarditis of interferon (IFN)gamma-deficient mice, suggesting that IL-17A plays a minimal role during acute myocarditis. In contrast, IL-17A-deficient mice were protected from postmyocarditis remodeling and did not develop DCM. Flow cytometric and cytokine analysis revealed an important role for IL-17A in heart-specific upregulation of IL-6, TNFalpha, and IL-1beta and the recruitment of CD11b(+) monocyte and Gr1(+) granulocyte populations into the heart. Furthermore, IL-17A-deficient mice had reduced interstitial myocardial fibrosis, downregulated expression of matrix metalloproteinase-2 and -9 and decreased gelatinase activity. Treatment of BALB/c mice with anti-IL-17A monoclonal antibody administered after the onset of myocarditis abrogated myocarditis-induced cardiac fibrosis and preserved ventricular function. CONCLUSIONS: Our findings reveal a critical role for IL-17A in postmyocarditis cardiac remodeling and the progression to DCM. Targeting IL-17A may be an attractive therapy for patients with inflammatory dilated cardiomyopathy.